Table 2.

Considerations for symptom management in patients with advanced CKD

Symptom	Initial Considerations for Management
Fatigue	Assess for modifiable contributing factors: vitamin D deficiency, metabolic acidosis, tertiary hyperparathyroidism, hypothyroid, anemia, mood disorders (depression, anxiety), sleep disorder, malnutrition, polypharmacy.
	Postdialysis fatigue: consider modifications to the dialysis prescription such as increased frequency.
	Consider low-intensity resistance and aerobic exercise where appropriate.
	Ensure the appropriate supports are in place to assist with activities of daily living and that nursing care is available where appropriate.
Sleep disorders	Assess for modifiable contributing factors and symptoms such as RLS, pruritus, pain, dyspnea, mood disorders (depression and anxiety), obstructive sleep apnea, medications.
	Consider nonpharmacologic management first: exercise if appropriate; cognitive and psychologic approaches (e.g., relaxation therapy, CBT); promote good sleep hygiene (avoid napping during the day, avoid stimulants such as caffeine, alcohol and nicotine in the evening).
	Consider pharmacologic therapy if nonpharmacologic interventions are unsuccessful and poor sleep is adversely affecting QOL: e.g., low dose gabapentin starting at 50–100 mg postdialysis (potentially also beneficial for RLS, neuropathic pain, and pruritus); melatonin; zaleplon 5–10 mg nightly; or doxepin 10 mg nightly.
RLS	Assess for modifiable contributing factors such as anemia and iron deficiency; medications such as dopamine antagonists, antidepressants (SSRIs, SNRIs, TCAs); calcium channel blockers, opioids.
	Consider nonpharmacologic management first: e.g., intradialytic aerobic exercise.
	Consider pharmacologic therapy if nonpharmacologic interventions are unsuccessful and RLS is adversely affecting QOL: e.g., low dose gabapentin starting at 50–100 mg postdialysis (potentially also beneficial for sleep, neuropathic pain, and pruritus); second-line options include nonergot derived dopamine agonists such as ropinirole at a starting dose of 0.25 mg/d and a maximum recommended dose of 3 mg/d.
Pruritus	Assess for modifiable contributing factors: anemia, iron deficiency, hypercalcemia, hyperphosphatemia, xerosis, allergies, drug sensitivities, contact dermatitis.
	Promote good skin care: avoid soap, but if used, use gentle soap; keep skin cool by wearing light and cool clothing; avoid excessive bathing or bathing in hot water and use emulsifying lotions in the bath; avoid scratching – keep fingernails short and encourage massage rather than scratching, wear gloves at night; maintain a humid home environment, especially in the winter.
	Topical emollients (moisturizers) are first-line treatment. They should have high water content and be free from fragrance and additives.
	Agents that help cool skin such as a fan, especially at night, or the use of topical camphor/menthol in the moisturizing base.
	Consider other topical therapies: gamma-linolenic acid 2.2% cream applied twice daily; capsaicin 0.025% or 0.03% ointment applied 2–4 times daily (may cause initial burning).
	Consider pharmacologic therapy if the above is unsuccessful and pruritus is adversely affecting QOL: e.g., low dose gabapentin starting at 50–100 mg postdialysis (potentially also beneficial for sleep, RLS, and neuropathic pain); second-line treatment – consider the TCA doxepin 10 mg nightly.
	Other therapies to consider with less evidence include UVB phototherapy ×3/wk and acupuncture.
Nausea and vomiting	Manage associated reversible symptoms such as constipation.
	Consider nonpharmacologic management: good oral hygiene; smaller, more frequent meals; minimize aromas; avoid foods that are greasy, spicy, or excessively sweet; relax in an upright position after eating to facilitate digestion; apply a cool, damp cloth to forehead or nape of neck; loose fitting clothing; complementary therapies such as relaxation, imagery, acupressure, or acupuncture.
	Consider pharmacologic therapy if the above is unsuccessful and nausea and vomiting are adversely affecting QOL: metoclopramide 2.5 mg PO/SC q4h PRN; ondansetron 4 mg PO ×3/d; haloperidol 0.5 mg PO/SC q4h PRN; olanzapine 2.5 mg PO q4h PRN.
Depressive symptoms	Manage associated reversible symptoms such as pain, poor sleep, pruritus.
	Assess and optimize social supports.
	Consider nonpharmacologic treatments: more frequent dialysis; CBT; exercise programs.
	Consider pharmacologic therapy with antidepressants if the above is unsuccessful and depressive symptoms are adversely affecting QOL.
Pain	Assess for modifiable contributing symptoms such as sleep and mood disorders (depression and anxiety).
	Consider nonpharmacologic management: exercise if appropriate; cognitive and psychologic approaches (e.g., relaxation therapy, CBT).
	If considering analgesics, establish whether pain is neuropathic or nociceptive in nature to direct analgesic approach.
	Adopt a step-wise approach to analgesics such as that outlined in the World Health Organization Analgesic Ladder.
	Analgesic selection, initial dosing, and titration must be individualized according to the patient’s health, previous exposure to analgesics, attainment of therapeutic goals, and predicted harms.
	Consider a trial of chronic opioid therapy if pain is moderate to severe, is having an adverse effect on function or QOL, and therapeutic benefits are likely to outweigh potential harm.
	Before initiating chronic opioid therapy, assess risks of substance abuse, misuse, or addiction.

RLS, restless legs syndrome; CBT, cognitive behavioral therapy; QOL, quality of life; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin and norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant; UVB = ultraviolet B; PO = by mouth; SC = subcutaneous; q4h = every 4 hours; PRN = when necessary.